1. Field of the Invention
The present invention relates to novel ruthenium catalysts and their use for performing carbon-carbon bond formation in aqueous media to produce useful biaryl compounds.
2. Description of the Related Art
Synthesis of biaryl moieties are of special interest as they are commonly found in many organic compounds including oils, drugs, flavors, petrochemicals, fragrances and food. For example, biphenyl moieties appear in many drug molecules such as losartan, valsartan, azilsartan, and anacetrapib, among others. Biaryls even appear in the liquid crystal mixture of commercial liquid crystal displays (LCD) as cyano-substituted biphenyl molecules containing long aliphatic tails. Biaryl moities are found in intermediate structures during the production of emulsifiers, optical brighteners, crop production products, and plastics. Substituted biphenyl structures are repeatedly found in natural products such as alkaloids and appear in numerous biologically active agents in pharmaceutical and agrochemical specialties. Polyaromatic compounds containing multiple aryl-aryl bonds possess original physical properties, which could lead to applications as organic conductors or semiconductors. Di- or tri-aromatic rings are also the backbone of ligands used for asymmetric catalysis.
Biaryl compounds are commonly prepared using well-known reactions such as the Suzuki and Stille couplings. These processes require one of the reaction partners to have either a boron or tin-bearing carbon, respectively, at the carbon where bond formation takes place. Alternatively, biaryl bonds may be formed using transition metal-catalyzed directed ortho functionalization and coupling. This process employs an aryl reactant bearing a substituent capable of directing transition metal insertion at the ortho position, thereby allowing bond formation between the site of metal insertion and a carbon atom on a reaction partner substituted with a suitable leaving group (e.g., a halide). Ortho DG's (Directing Groups) are strong coordinating or chelating groups that have the effect of increasing the kinetic acidity of protons in the ortho-position.
Typically, transition metal-catalyzed ortho C—H functionalization and coupling are achieved in N-methylpyrrolidinone (NMP), dimethylformamide (DMF), dimethylacetamide (DMAc), or similar solvents. These solvents are undesirable because of their toxicity and/or high boiling points. Also, coupling reactions with transition metals are often carried out under inert atmosphere, such as with a Schlenk tube, due to sensitivity of the catalyst to the ambient atmosphere. Thus, because of disposal and toxicity issues, and general ease in handling and manipulation, there is an interest in finding more environmentally friendly processes for forming biaryl bonds by transition metal-catalyzed ortho C—H functionalization and coupling.